Differential effects of ibuprofen and indomethacin on cerebral oxygen kinetics in the very preterm baby

Michael J Stark; Tara M Crawford; Nina M Ziegler; Anthea Hall; Chad C Andersen

doi:10.3389/fped.2022.979112

Differential effects of ibuprofen and indomethacin on cerebral oxygen kinetics in the very preterm baby

Front Pediatr. 2022 Oct 3:10:979112. doi: 10.3389/fped.2022.979112. eCollection 2022.

Authors

Michael J Stark^{1

2}, Tara M Crawford², Nina M Ziegler¹, Anthea Hall², Chad C Andersen^{1

2}

Affiliations

¹ Department of Neonatal Medicine, The Women's and Children's Hospital, North Adelaide, SA, Australia.
² Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.

Abstract

Background: Ibuprofen is preferred to indomethacin for treatment of a significant patent ductus arteriosus (PDA) in preterm babies despite indomethacin being associated with a lower risk of intraventricular haemorrhage. This difference is thought to relate to the discrepant effects of each medication on cerebral oxygen kinetics yet the effect of ibuprofen on cerebral perfusion is uncertain.

Methods: Forty-eight babies < 30 weeks with a significant PDA, defined by echocardiography, were randomly assigned to either indomethacin or ibuprofen (n = 24 per group) and stratified by gestation and chronologic age. Cerebral blood flow [total internal carotid blood flow (TICF)] and oxygen physiology [oxygen delivery (modCerbDO₂) and consumption (modCerbVO₂)] were measured using cranial Doppler ultrasound and near-infrared spectroscopy, and cerebral oxygen extraction (cFTOE) calculated, immediately before and following administration. Temporal and treatment related changes were analysed.

Results: A fixed effect of time was seen for TICF (p = 0.03) and therefore modCerbDO₂ (p = 0.046) and cFTOE (p = 0.04) for indomethacin alone. In the indomethacin group, TICF and modCerbDO₂ fell from baseline to 5 and 30 min respectively (TICF p < 0.01, cDO₂ p = 0.01) before increasing from 5 min to 24 h (p < 0.01) and 30 min and 24 h (p < 0.01) timepoints. cFTOE peaked at 30 min (p = 0.02) returning to baseline at 24 h. There was a parallel increase in arterial lactate.

Conclusion: Indomethacin significantly reduces cerebral blood flow soon after administration, resulting in a parallel increase in oxygen extraction and arterial lactate. This implies that the balance of oxygen kinetics at the time of treatment may be critical in very preterm babies with significant PDA.

Keywords: fractional oxygen concentration; ibuprofen; indomethacin; oxygen consumption; oxygen delivery; patent ductus arterious; preterm neonate.